Pharmacogenetics of citalopram-related side effects in children with depression and/or anxiety disorders

Abstract

Pharmacogenetic approach to antidepressant (AD) response is a promising avenue toward individualizing AD treatment. This is particularly relevant in pediatric populations because of concerns about the suicide risk of serotonin selective reuptake inhibitors (SSRIs), resulting in a black-box warning. However, to date, no specific gene or polymorphism has been consistently implicated as a marker of AD side effect (SE) in the pediatric population. The aim of this study was to examine the association between polymorphisms in genes related to the serotonergic system and citalopram SE's in children and adolescents with major depressive disorder (MDD)/dysthymia and/or anxiety disorders. Outpatients (N = 87, 44 % males), aged 7-18 years with a DSM-IV-TR diagnosis of MDD/dysthymia and/or an anxiety disorder were treated in an 8-week open trial with 20-40 mg/day of citalopram. SE's were rated using a questionnaire devised specifically for this study. Association analysis between known/candidate genetic variants in three genes (5-HTR2A, 5-HTR1Dβ, 5-HTR2C) and SE's was conducted. Agitation was more common in boys than girls (male:female 42.1 vs. 18.7 %, χ = 5.61, df = 1, p = 0.018). Subjects with 5-HTR1Dβ CC genotype showed more agitation vs. both CG and GG genotypes (CC:CG:GG 71.4 vs. 33.3 vs. 18.1 %, χ = 8.99, df = 2, p = 0.011). The 5-HTR1Dβ CC genotype was associated with more reports of agitation. It has been suggested that agitation may be an intermediate phenotype to suicidal behavior. Thus, it seems that 5-HTR1Dβ polymorphism may be involved in citalopram-related agitation in children and adolescents treated for depression and/or anxiety.

Antidepressant-Induced Activation in Children and Adolescents: Risk, Recognition and Management

“…Only the 5-HTR1Dβ G861C was associated with and increased risk of activation, with the CC genotype experiencing significantly more agitation (71.4%) compared to the CG (33%) and GG (18.1%) genotypes ( p =0.02). 49…”

“…The complex pathophysiology of antidepressant-induced activation likely involves genetic and neurochemical factors as well as circuit-level processes that interact with psychological and pharmacologic aspects of the patient and treatment (Figure 3). 49 However, given the difficulty assessing and defining activation, it is not surprising that it has been difficult to elucidate the pathophysiology of activation with clarity. Some hypothesize that activation—like affective instability—represents a variant of the manic phase of bipolar disorder.…”

PLGA Microsphere Addition to 1‐Hydroxy‐2‐napthoic Acid Enhances the Sustained Release of Escitalopram

“…Here, we used escitalopram (ET), an antidepressant, which is a selective serotonin reuptake inhibitor in the brain cells . ET has serious side effects such as nausea, dry mouth, sleep disturbance, constipation, fatigue, drowsiness, and dizziness, resulting in patients needing to gradually increase the therapeutic dose . Furthermore, in patients with depression, it is inconvenient to take antidepressant medication every day.…”

Clinical Pharmacogenetics of Cytochrome P450-Associated Drugs in Children

“…As with sertraline, both drug labels include a black box warning due to increased risk for suicidal thinking and behavior in young patients. Both drugs are frequently used off-label in children with depression, anxiety, obsessive–compulsive disorder, autism, and/or pervasive developmental disorders [ 38 , 89 , 94 ].…”